Lactose Samples Research Articles

Changes of Unit Cell Parameters in Lactose Saturated by Substances Technologically Processed by Dilution

Background: Our research investigates how the structure of a lactose matrix can be altered by the specific drugs used to saturate it. In particular, we examine whether ultra-high dilutions of substances, such as antibodies, can change the crystal structure of lactose. Methods: We employed methods including X-ray diffractometry, Raman spectroscopy, and granulometric content analysis. Results: Our findings suggest that once saturated with highly diluted substances, lactose does indeed gain and retain changes in its crystalline structures [particularly cell parameters a, b, c, β]. These changes are most pronounced between intact and saturated lactose samples, and there are also differences observed when using different solutions for saturation. Conclusion: The results support the idea that ultra-high dilutions can irreversibly change the structure of lactose, potentially due to differences in solution wetting and subsequent recrystallization of the lactose matrix.

Phase-sensitive optical coherence tomography reveals droplet penetration into a powder bed

Understanding the mixing behavior that unfolds when liquid droplets impact on powder beds requires a sub-surface dynamic imaging method that provides high spatial and temporal resolution. In this study, a high-resolution phase-sensitive optical coherence tomography (PhS-OCT) technique was introduced to provide in-depth insights into the interaction of droplets and powder beds. A theoretical model correlating changes in the optical path differences (OPD) of the OCT signal with physical properties of the powder bed was presented. Experiments were conducted on three powders with median particle diameters, i.e., the size corresponding to the 50th percentile of the cumulative volume distribution, of 3 µm (mannitol), 4 µm (mannitol) and 109 µm (SV010). Water and ethanol droplets were used to illustrate the technique. The results demonstrated that OPD maps can qualitatively resolve the liquid-powder mixture region, both temporally and spatially, as the droplet diffuses into the powder bed, allowing for a quantitative description of diffusion behavior. A comparison of lactose and mannitol powder samples revealed varying diffusion rates, potentially attributed to differences in porosity, particle size, and agglomeration. Additionally, water and ethanol droplets exhibited significantly different (p = 0.005) diffusion profiles for the same powder properties. In general, the findings indicate the potential of the proposed PhS-OCT technique for evaluating the mixing behavior of multi-phase mixtures, holding promise in applications such as pharmaceutical drug formulations and additive manufacturing.

Multicenter project Brazil-Italy: physicochemical analysis of Zincum metallicum and lactose in dynamized mixtures

Background: The use of sensitive techniques can be useful to increase the understanding of homeopathic systems behavior. 
 Aim: To analyze physicochemical properties of Zincum metallicum and lactose mixtures prepared according to Brazilian Homeopathic Pharmacopeia.
 Methodology: Zincum metallicum was prepared using lactose as vehicle, from 1 to 3 cH, and from 1 to 6dH. All samples including respective controls (dynamized lactose) were analyzed by Atomic Absorption Spectroscopy (AAS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM) with X-Ray Energy Dispersive Spectroscopy (EDX), Scanning Electron Microscopy (SEM), and Differential Scanning Calorimetry (DSC).
 Results: AAS analysis showed the dynamization process decreases zinc concentration in a proportional manner to the increase of homeopathic potencies. Quantities of 4ppm and 132 ppm of zinc were detected in 6dH and 3cH, respectively. XRD analysis showed crystalline form of lactose was not modified by dynamization. Amorphous lactose spheres were observed by TEM in all samples, with mean size ranging from 800 to 200 nm. EDX obtained in the TEM confirmed zinc presence throughout the amorphous matter and the absence of individualized zinc crystalline particles. These results are in accordance with XRD which showed absence of zinc diffraction peaks, in all lactose samples containing zinc suggesting this metal could be modified from crystalline to amorphous state, and consequently adsorbed into lactose molecules. SEM structural analysis of lactose and zinc (1cH) samples using BSE detector showed no zinc metal grains confirming XRD and TEM results. DSC analyses presented statistical significance differences (p

Drugs in ultra-high dilution induce changes in the enthalpy associated with loss of crystallization water in lactose

Drugs in ultra-high dilution (UHD) are used in homeopathy. Lactose is used as a binding medium for UHD drugs. FTIR and Raman spectroscopy revealed that although devoid of molecules of the starting substance, different UHD drugs exhibit different amounts of free water molecules and variation in hydrogen bond strength. The aim of the present study was to establish whether specific water structures in UHD could specifically modify the water structure in lactose, particularly the water of crystallization. 3 UHD’s (potencies), 30cH, 200cH and 1000cH, of 2 drugs, Natrum muriaticum and Sulphur were mixed to lactose samples separately. Differential scanning calorimetry (DSC) of the samples was measured. The thermograms of potencies mixed to lactose differed from each other with respect to temperature and enthalpy associated with the removal of water of crystallization from lactose. We believe that the tested UHD modified the water structure in lactose thereby changing the enthalpy for the removal of water of crystallization. Different levels of thermal energy are needed to remove both free water molecules and water of crystallization from lactose. UHD’s also contributed to the change in enthalpy associated with the removal of water of crystallization from lactose. The tested UHD might have modified the number and strength of hydrogen bonds in the crystal structure of lactose. Specific water structures in liquid aqueous ethanol medium are transferable to the solid medium(lactose).

Optimizing the immobilization conditions of β-galactosidase on UV-cured epoxy-based polymeric film using response surface methodology.

UV-cured epoxy-based polymeric film was prepared from glycidyl methacrylate, trimethylolpropane triacrylate, and poly(ethylene glycol) methylether acrylate. 2-hydroxy-2- methylpropiophenone was used as photo initiator. Covalent binding through epoxy groups was employed to immobilize β-galactosidase from Escherichia coli onto this film, and immobilization conditions were optimized by the response surface methodology. ATR-Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) analysis was carried out to characterize the epoxy-based polymeric film. Immobilization yield of β-galactosidase on the material was calculated as 3.57mg/g and the highest enzyme activity for the immobilized enzyme recorded at pH 6.5°C and 60°C. The immobilized enzyme preserved 51% of its activity at the end of 12 runs. Free and immobilized enzyme hydrolyzed 163.8 and 172.3µM lactose from 1% lactose, respectively. Kinetic parameters of both free and immobilized β-galactosidase were also investigated, and Km values were determined to be 0.647 and 0.7263mM, respectively. PRACTICAL APPLICATIONS: In our study we prepared a UV-cured epoxy-based polymeric film and optimized the immobilization conditions of β-galactosidase from Escherichia coli onto this polymeric film by using response surface methodology (RSM). For this purpose, three-level and three-factor Box-Behnken design, which is an independent, rotatable or nearly rotatable, quadratic design, was applied. Optimal levels of three variables, namely, the amount of enzyme, immobilization time, and pH were determined using Box-Behnken experimental design. Lactose hydrolysis studies were performed from milk and lactose samples using free and immobilized enzyme. In addition, kinetic parameters, storage stability, and re-usability of immobilized β-galactosidase were examined.

Spray drying lactose from organic solvent suspensions for aerosol delivery to the lungs.

Lactose is widely used as an approved excipient for dry powder inhaler (DPI) products. Spray drying technique is a rapid method for converting a liquid feed into inhalable dried particles. However, spray-dried (SD) lactose powders produced from solutions are mostly amorphous and particularly unstable when exposed to moisture. In the present study, we explored the use of spray drying suspensions containing crystalline lactose particles in an organic solvent, and investigated the physicochemical properties of the resulting powders. The solution formulation was spray dried as a control. Two conditioned crystalline lactose samples were used for suspension formulations: Lactohale (LH) 300 lactose and jet-milled (JM) lactose micronized from LH300. The suspension formulations each contained 12mg/ml suspended crystalline lactose particles (either LH300 or JM lactose) in isopropyl alcohol. The solution formulation contained 60mg/ml lactose in water. The SD powders were stored under 25°C/60% RH and 40°C/75% RH for 3months. The particulate properties and in vitro dispersion performance were examined at various time points. The SD lactose obtained from solution recrystallized and was no longer dispersible after 1-day storage at both storage conditions. The suspension SD JM lactose powder showed deterioration in the particulate properties and dispersibility over time, but more gradually. In contrast, the SD LH300 powder was stable, with its particulate properties and dispersion performance (FPF: ~12%) remaining the same after 3-months storage at 25°C/60% RH. The SD LH300 stored at 40°C/75% RH showed no change in particulate properties, but the FPF decreased over 3months. Overall, SD lactose powders obtained from suspension demonstrated superior stability performance compared to SD lactose obtained from solution.

Presence of Pesticides in Milk and Infant Formulas Produced in Pegah Dairy Plants, Iran

ersistent Organic Pollutants (POPs) are bioaccumulative toxic chemicals that long-lasting in the environment and accumulate in the food chain during movement. The organochlorine pesticides (OCP) effect on birth defects, neurological, behavioral effects, affect reproductive processes, alter the immunological response, endocrine disruptors and cancer. In this study was measured the content of organochlorine pesticides in 40 samples of milk, baby oil, lactose, whey protein and infant milk formulas produced in the Pegah dairy plants Iran in 2018 to 2019. The determination was done using gas chromatography in accordance with the instructions delineated by the International Dairy Federation. The result showed, the whey protein, lactose, baby oil and infant formula samples that all mean residual values of chlorinated pesticides in all samples were lower than LOD detection limits. The results of infant formula analysis showed that residual concentration of chlorinated pesticides was lower than the maximum residual value recommended by the FAO/WHO.

Performance of Commercial Colorimetric Assays for Quantitation of Total Soluble Protein in Thermally Treated Milk Samples

Commercial colorimetric protein assays have been widely used, but their performance for protein quantitation in thermally processed milk samples has not been investigated. This study evaluated four colorimetric assays for quantitation of soluble protein in nonfat milk samples that were subjected to different degrees of heat treatment. Copper ion-based Pierce™ bicinchoninic acid protein assay (BCA) and Pierce™ modified Lowry protein assay (modified Lowry) consistently registered higher protein levels than those determined by dye binding-based Pierce™ Coomassie Plus (Bradford) assay (Coomassie Plus) or Pierce™ 660-nm protein assay (660-nm). When milk samples were autoclaved or dry-heated at ≥ 121 °C for 10 min, reduction in soluble protein content was reflected in measurements of Coomassie Plus and 660-nm assays but was not indicated by BCA or modified Lowry assays. In samples dry-heated at 176 °C, while no protein was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Coomassie Plus or 660-nm, BCA, and modified Lowry indicated protein levels that were 215.7 and 79.4%, respectively, of those of unheated samples. Analysis of lactose samples showed that lactose may contribute to a 13.4 or 1.0% overestimation in BCA or modified Lowry measurement of protein content in unheated dry milk samples. This study demonstrated that quantitation of protein in thermally treated milk samples using copper ion-based BCA and modified Lowry assays could be significantly affected by lactose and, to a greater degree, other reducing substances formed during heating likely via the caramelization and Maillard reaction pathways. In contrast, dye binding-based Coomassie Plus and 660-nm assays were not affected and may be more accurate for measurement of protein content in thermally treated milk samples.

Exploring the impact of extrinsic lactose fines, a USP modified sampling device and modified centrifuge tube on the delivered dose uniformity and drug detachment performance of a fluticasone propionate dry powder inhaler

The present study aimed to probe influences exerted by extrinsic lactose fines on drug detachment and delivered dose uniformity (DDU) of fluticasone propionate (FP) dry powder inhaler (DPI). Extrinsic lactose fines (0–35%) containing lactose pre-blends were formulated using a low shear 3D shaker mixer and systematically analyzed for various physicochemical properties. Moreover, formulated FP DPIs were assessed for drug detachment by force distribution concept and the DDU using two different sampling devices i.e. the Dosage Unit Sampling Apparatus (DUSA) and USP modified glass sampling device (modified DUSA) coupled with Aerolizer® device at 60 L/min. The physicochemical assessment of control and pre-blend lactose samples displayed significant differences in particle size, surface roughness, degree of surface irregularity and powder flow properties. The formulated FP DPIs displayed monolayer-type FP distribution across the lactose particles in laser Raman spectroscopy with acceptable content uniformity (~100%). Drug detachment study using a modified centrifuge tube showed significant differences in drug detachment profile. The FP DPI formulated using 20% of lactose fines showed the lowest drug detachment force (349.45 gf) as compared to the other lactose samples. Moreover, the FP DPI formulated using 20% of lactose fines demonstrated acceptable mean delivered dose (107.76 and 110.62 μg) with the lowest coefficient of variation using DUSA and modified DUSA, respectively. The present study is the first comprehensive summary of delivered dose uniformity using two different USP sampling devices. Accordingly, these observations may be of high significance for both intuitional and industrial formulators.

A study on the caking behaviour of binary mixtures of lactose due to solid-state crystallisation of the amorphous phase

This work deals with caking behaviour of lactose monohydrate powders containing small amounts of amorphous lactose. The objective was to elucidate the relation between the caking ability of powder mixtures and the crystallisation behaviour of amorphous lactose. Binary mixtures consisting of amorphous lactose and α-lactose monohydrate were prepared and tested using an accelerated caking test. Amorphous lactose samples were prepared using the freeze-drying process. Two caking devices were developed to characterize the caking ability of powders. The effect of amorphous content, relative humidity, temperature and pressure on the caking behaviour of samples was investigated. The results showed that the presence of even small amounts of amorphous lactose (as low as 0.125%) could cause caking. The more influencing parameters were found to be the relative humidity and the temperature whereas the pressure had no significant effect. The caking behaviour was shown to be closely linked with crystallisation extent and kinetics. A dimensionless time based on Avrami model for crystallisation rate was defined allowing unifying the experimental data.

Variability in the α and β anomer content of commercially available lactose

Lactose, a disaccharide is a ubiquitous excipient in many pharmaceutical formulations which exists in two anomeric forms; either as α- or β-lactose. The anomers have different properties which can affect their application. Nevertheless, batches of lactose products are widely produced by many manufacturers, and is available in many grades. However, the anomeric content of these batches has not been accurately characterized and reported previously. Therefore, the aim of this study was to analyse a set of 19 commercially available samples of lactose using a novel H1-NMR technique to establish a library showing the anomeric content of a large range of lactose products. The lactose samples were also analysed by DSC. The anomeric content of the α-lactose monohydrate samples were found to vary by more than 10%, which might influence bioavailability from final formulations. The data showed that there is a need to determine and monitor the anomeric content of lactose and this should be a priority to both the manufacturers and the formulators of medicines.

Modification of α-lactose monohydrate as a direct compression excipient using roller compaction

Roller compaction was used to prepare a direct-compressed lactose excipient using crystalline α-lactose monohydrate. The effect of various roller compaction process parameters (compaction pressure, compaction repetition, and speed ratio) on the characteristics of compacted α-lactose monohydrate was investigated. Results were compared with data obtained using industrial spray-dried lactose and lactose samples with different degrees of crystallinity. XRPD analysis revealed that roller compaction reduced the crystallinity of α-lactose monohydrate, and the resulting material is similar to spray-dried lactose in behavior as a direct compression excipient. Roller compaction introduced desirable characteristics to the raw α-lactose monohydrate by inducing changes in crystallinity and particle morphology. Scanning electron microscopy results indicated that the compaction process converted some of the original torpedo-shaped crystals of α-lactose monohydrate into a more cylindrical shape with rounded edges. Compaction pressure and repetition of compaction have a significant effect on the modification of the crystallinity of the processed, raw α-lactose monohydrate.

Short communication: Sensitive detection of norbixin in dried dairy ingredients at concentrations of less than 1 part per billion

Norbixin is the water-soluble carotenoid in annatto extracts used in the cheese industry to color Cheddar cheese. The purpose of norbixin is to provide cheese color, but norbixin is also present in the whey stream and contaminates dried dairy ingredients. Regulatory restrictions dictate that norbixin cannot be present in dairy ingredients destined for infant formula or ingredients entering different international markets. Thus, there is a need for the detection and quantification of norbixin at very low levels in dried dairy ingredients to confirm its absence. A rapid method for norbixin evaluation exists, but it does not have the sensitivity required to confirm norbixin absence at very low levels in compliance with existing regulations. The current method has a limit of detection of 2.7 μg/kg and a limit of quantification of 3.5 μg/kg. The purpose of this study was to develop a method to extract and concentrate norbixin for quantification in dried dairy ingredients below 1 μg/kg (1 ppb). A reverse-phase solid-phase extraction column step was applied in the new method to concentrate and quantify norbixin from liquid and dried WPC80 (whey protein concentrate with 80% protein), WPC34 (WPC, 34% protein), permeate, and lactose. Samples were evaluated by both methods for comparison. The established method was able to quantify norbixin in whey proteins and permeates (9.39 μg/kg to 2.35 mg/kg) but was unable to detect norbixin in suspect powdered lactose samples. The newly developed method had similar performance to the established method for whey proteins and permeates but was also able to detect norbixin in powdered lactose samples. The proposed method had a >90% recovery in lactose samples and a limit of detection of 28 ppt (ng/kg) and a limit of quantification of 94 ppt (ng/kg). The developed method provides detection and quantification of norbixin for dairy ingredients that have a concentration of <1 ppb.

Structural and thermal analyses of zinc and lactose in homeopathic triturated systems

A series of different experimental approaches was applied in Zincum metallicum (Zinc met.) samples and lactose controls. Experiments were designed to elucidate the effect of zinc trituration and dynamization on physicochemical properties of homeopathic formulations, using lactose as excipient. Zinc met. potencies (Zinc met 1-3c) were triturated and dynamized using lactose as excipient, according to Brazilian Homeopathic Pharmacopoeia. Lactose samples (LAC 1-3c) were also prepared following the same protocol and used as controls. The samples were analyzed structurally by Atomic Absorption Spectroscopy (AAS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM) with Energy Dispersive X-ray Spectroscopy (EDX) and Scanning Electron Microscopy (SEM), and thermodynamically by Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC). AAS analysis detected 97.0 % of zinc in the raw material, 0.75 % (Zinc met 1c) and 0.02% (Zinc met 2c). XRD analysis showed that inter-atomic crystalline spacing of lactose was not modified by dynamization. Amorphous and crystalline lactose spheres and particles, respectively, were observed by TEM in all samples, with mean size from 200 to 800nm. EDX obtained with TEM identified zinc presence throughout the amorphous matter but individualized zinc particles were not observed. SEM images obtained from dynamized samples (LAC 1c and Zinc met 1c) with electron backscattering could not identify zinc metal grains. The dynamization process induced Derivatives of Thermal Gravimetric (DTg) peak modification, which was previously centered near 158°C to lactose, to a range from 140 to 170°C, suggesting the dynamization process modifies the temperature range of water aggregation. Thermal phenomena were analyzed and visualized by Analysis of Variance (ANOVA) and Principal Component Analysis (PCA) statistics. Both indicated that fusion enthalpy of dynamized samples (DynLAC 1-3c; DynZn 1-3c) increased 30.68J/g in comparison to non-dynamized lactose (LAC; p<0.05). Our results suggested no structural changes due to the trituration and dynamization process. However, TG and DSC analyses permit the differentiation of dynamized and non-dynamized groups, suggesting the dynamization process induced a significant increase in the degradation heat. These results call for further calorimetric studies with other homeopathic dilutions and other methodologies, to better understand the dynamics of these systems.

Determination of Interfacial Amorphicity in Functional Powders.

The nature of the surfaces of particles of pharmaceutical ingredients, food powders, and polymers is a determining factor for their performance in for example tableting, powder handling, or mixing. Changes on the surface structure of the material will impact the flow properties, dissolution rate, and tabletability of the powder blend. For crystalline materials, surface amorphization is a phenomenon which is known to impact performance. Since it is important to measure and control the level of amorphicity, several characterization techniques are available to determine the bulk amorphous content of a processed material. The possibility of characterizing the degree of amorphicity at the surface, for example by studying the mechanical properties of the particles' surface at the nanoscale, is currently only offered by atomic force microscopy (AFM). The AFM PeakForce QNM technique has been used to measure the variation in energy dissipation (eV) at the surface of the particles which sheds light on the mechanical changes occurring as a result of amorphization or recrystallization events. Two novel approaches for the characterization of amorphicity are presented here. First, since particles are heterogeneous, we present a methodology to present the results of extensive QNM analysis of multiple particles in a coherent and easily interpreted manner, by studying cumulative distributions of dissipation data with respect to a threshold value which can be used to distinguish the crystalline and amorphous states. To exemplify the approach, which is generally applicable to any material, reference materials of purely crystalline α-lactose monohydrate and completely amorphous spray dried lactose particles were compared to a partially amorphized α-lactose monohydrate sample. Dissipation data are compared to evaluations of the lactose samples with conventional AFM and SEM showing significant topographical differences. Finally, the recrystallization of the surface amorphous regions in response to humidity was followed by studying the dissipation response of a well-defined surface region over time, which confirms both that dissipation measurement is a useful measure of surface amorphicity and that significant recrystallization occurs at the surface in response to humidity.

A titration approach to identify the capacity for starch digestion in milk-fed calves

Calf milk replacers (MR) commonly contain 40% to 50% lactose. For economic reasons, starch is of interest as a lactose replacer. Compared with lactose, starch digestion is generally low in calves. It is, however, unknown which enzyme limits the rate of starch digestion. The objectives were to determine which enzyme limits starch digestion and to assess the maximum capacity for starch digestion in milk-fed calves. A within-animal titration study was performed, where lactose was exchanged stepwise for one of four starch products (SP). The four corn-based SP differed in size and branching, therefore requiring different ratios of starch-degrading enzymes for their complete hydrolysis to glucose: gelatinised starch (α-amylase and (iso)maltase); maltodextrin ((iso)maltase and α-amylase); maltodextrin with α-1,6-branching (isomaltase, maltase and α-amylase) and maltose (maltase). When exceeding the animal’s capacity to enzymatically hydrolyse starch, fermentation occurs, leading to a reduced faecal dry matter (DM) content and pH. Forty calves (13 weeks of age) were assigned to either a lactose control diet or one of four titration strategies (n=8 per treatment), each testing the stepwise exchange of lactose for one SP. Dietary inclusion of each SP was increased weekly by 3% at the expense of lactose and faecal samples were collected from the rectum weekly to determine DM content and pH. The increase in SP inclusion was stopped when faecal DM content dropped below 10.6% (i.e. 75% of the average initial faecal DM content) for 3 consecutive weeks. For control calves, faecal DM content and pH did not change over time. For 87% of the SP-fed calves, faecal DM and pH decreased already at low inclusion levels, and linear regression provided a better fit of the data (faecal DM content or pH v. time) than non-linear regression. For all SP treatments, faecal DM content and pH decreased in time (P<0.001) and slopes for faecal DM content and pH in time differed from CON; P<0.001 for all SP), but did not differ between SP treatments. Faecal DM content of SP-fed calves decreased by 0.57% and faecal pH by 0.32 per week. In conclusion, faecal DM content and pH sensitively respond to incremental inclusion of SP in calf MR, independently of SP characteristics. All SP require maltase to achieve complete hydrolysis to glucose. We therefore suggest that maltase activity limits starch digestion and that fermentation may contribute substantially to total tract starch disappearance in milk-fed calves.

Recrystallization behavior of amorphous and crystalline lactose from TSPDF

Lactose is a disaccharide sugar of galactose and glucose that is most commonly associated with milk. Its importance to the food and animal product industry cannot be overstated, as it is involved in aspects as diverse as baking, confectionary, and infant products. The other major use of lactose is in the pharmaceutical industry. The mildly sweet and loosely bland flavor of lactose has lent to its use as a stabilizer and excipient in pharmaceutical products. Despite the wide range of applications for this material, there is still much to be studied. While it is known to exist in several crystalline forms and as two anomers, α and β, characterized by the flipping of a hydroxide group on the glucose ring, the amorphous form of lactose is less understood. Yet it is this amorphous form which may play a crucial role in the physicochemical stability of amorphous drug dispersions. In order to fully understand the structural changes which lactose undergoes when converted from a crystalline to amorphous material, total scattering experiments coupled with PDF analysis for structural identification of amorphous lactose of different origins were undertaken with the goal of understanding the recrystallization behavior of this versatile material. Samples measured included commercial forms of lactose, crystalline and amorphous, and amorphous forms obtained by melt quenching and lyophilization. Recrystallization was followed for the amorphous forms by measuring characteristic samples aged at 400C/75% RH, which is a standard condition for stressing pharmaceutical materials to extrapolate shelf-life. By fitting the PDF curves to a structural model of lactose, and refining with the characteristic function for a sphere of radius r, an estimate of the coherence length of atom-atom correlations for a give sample provides a measure of the growth progression, from single molecule to crystallite for the lactose samples. Coupled with data from NMR spectroscopy, TSPDF analysis is teasing out the nuances of the recrystallization behavior of lactose.

Quantitation of α-Lactalbumin by Liquid Chromatography Tandem Mass Spectrometry in Medicinal Adjuvant Lactose.

Lactose is a widely used pharmaceutical excipient, sometimes irreplaceable. Traces of residual proteins left during production of lactose are potential allergen to body. The present paper describes a sensitive and specific LC-MS method for the determination of α-lactalbumin (α-La) in lactose samples. Chromatographic separation was performed on an Acquity UPLC BEH300 C18 column (2.1 × 150 mm, 1.7 μm) with an isocratic mobile phase consisting of water containing 0.1% TFA and acetonitrile containing 0.1% TFA (80 : 20, v/v). Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an ESI interface operating in positive ionization mode. Quantitation was performed using selected ion monitoring of m/z 2364 for α-La. The calibration curve was linear from 0.2 to 10 µg/mL. The intra- and interday precisions were less than 7.6% and the accuracy ranged from 96.4 to 104.5%. The limit of quantification (LOQ) was 0.15 µg/mL and the limit of detection (LOD) was 0.05 µg/mL. This method was then successfully applied to investigate 6 different lactose samples. The application can provide technical preparation for the development of specification of lactose.

Importance of particle size and shape on the tensile strength distribution and de-agglomeration of cohesive powders

PurposeThe purpose of the study was to understand the role of particle size and shape changes in modifying agglomerate strength distribution and de-agglomeration of cohesive lactose powders. MethodsThe relative de-agglomeration of three lactoses of different particle size distributions (Lactohale 201 or LH201, Lactohale 210 or LH210 and Lactohale 220 or LH220) was determined from laser diffraction particle sizing of the aerosol plume at different air flow rates. The agglomerate strength distributions were estimated by Monte Carlo simulation using the primary particle size, work of cohesion and tapped density distributions determined by laser diffraction, inverse gas chromatography and tapping apparatus, respectively. The morphology and particle shape parameters were determined by scanning electron microscopy and the Morphologi G3. ResultsThe estimated agglomerate strength correlated well with the de-agglomeration of all lactose samples at different air flow rates. While the work of cohesion of the lactose samples was not significantly different, the packing fraction was dependent on the proportion and shape of intermediate-sized, cohesive particles between 5.4 and 14μm. For example, while the proportion of particles <5.4μm was similar for all lactose samples, the proportion of intermediate-sized, cohesive particles increased in the order of LH201<LH210<LH220. The intermediate-sized, cohesive particles were more elongated than the <5.4μm fraction and the extent of elongation of the lactose samples increased in the order of LH220>LH210>LH201. ConclusionThe study reinforced the role of agglomerate strength distributions in understanding de-agglomeration of cohesive materials. Modification of particle size distributions and shape characteristics contributed to the agglomerate strength changes in the lactose samples. The study enhanced the fundamental understanding of powder de-agglomeration and provided strategic approaches that could be used to improve inhalation product performance.

The effect of solvent treatment on the performance of various carriers in dry powder inhalations containing salbutamol sulphate.

Objective(s) : It has been suggested that the efficiency of dry poder inhaler (DPI) is generally low. Therefore, the aim of the present research work was to use the solvent treatment of the carrier in DPIformulations to see the possibility of inducing desirable characteristics. Lactose sieve fractions of 63-90 µm were submerged in ethanol or 80% v/v ethanol, methanol or propanol. Lactose crystals were then blended with either 1% w/w or 4% w/w salbutamol sulphate using a Turbula mixer. Drug detachment was studied using a multistage liquid. Laser particle size analyzer, DSC, and pycnometer were used to characterize the treated lactose and mannitol samples. SEM was used to study surface morphologies. In case of mannitol as a carrier only ethanol was used as a solvent. SEM images displayed less rugosities and increased surface smoothness after submersion. Although the tomahawk like shape remained fairly constant in most lactose samples, the solvent treatment changed the shape of mannitol particles which was proved by SEM results. Deposition results showed that the type of solvent had an influence on fine particle fraction. In addition, the payload had also a big impact on fine particle fraction values. Generally, treated samples showed better performance compared to untreated samples. Solid state analysis by DSC showed that no major changes occurred in the treated samples compared to untreated samples. The solvent treated method can be used as an approach to improve the performance of carriers such as lactose and mannitol in dry powder inhaler.